RX511 Antibiotic Inhibitors of Protein Synthesis 2

Which sugar group anchors macrolides to their target site?

Desosamine (top)

Which sugar group contributes hydrophobic contacts that help orient macrolides within the binding site?

Cladinose (bottom)

How do macrolides work?

- Bind to 50S subunit

- Block exit site

- Bacteriostatic

- One of the best classes for atypicals

What are the issues with erythromycin?

- Solubility

- Acid-labile

- Metabolically susceptible

What are the key points of erythromycin lactobionate?

- Preferred for serious infections

- Infuse slowly and dilute properly

What are the key points of erythromycin with stearic acid?

- Increases absorption and acid protection

- Lowers dose variability

What are the key points of erythromycin with ethylsuccinate?

- Increases acid stability

- Available as a suspension

- Lowers absorption variability

What are the key points of erythromycin estolate?

- Best and most consistent oral bioavailability

- Hepatotoxic

What are the pharmacokinetic issues of erythromycin?

- Enteric coating or prodrug needed for oral administration

- Inconsistent oral absorption

- Stearate salts are better absorbed when fasting

- Ethylsuccinate esters are better absorbed with food

- 2-hour half-life, given 4 times a day

- Self-degradation in acidic conditions

What are the key points of clarithromycin?

- Partially retains motilin agonism

- Superior lung and alveolar macrophage penetration

- Given 2 times a day

- Treats H. pylori-associated duodenal ulcers

- Treats acute exacerbations of chronic bronchitis

What are the key points of azithromycin?

- Substantially reduces motilin agonism

- Given once daily

- Treats otitis media

What do clarithromycin and azithromycin both treat?

- Mycobacterium avium complex in advanced AIDS patients

- Community-acquired pneumonia

- Sinusitis

How do bacteria resist macrolides?

Binding site mutations

How do tetracyclines work?

- Bind 30S subunit near 16S rRNA

- Reversible

- Bacteriostatic

What are the uses of tetracyclines?

- Tick-borne illnesses (BLATER)

- Community-acquired MRSA

- STIs

- Malaria prophylaxis

- Anthrax

What are the important considerations of tetracyclines?

- Do not take with metal ion supplements

- Hydroxyl group at C6 is unstable in acidic and basic conditions

- Epimerization (taking expired) leads to Fanconi syndrome

Fanconi syndrome

A form of kidney failure that prevents the reabsorption of nutrients caused by expired tetracyclines

How do bacteria resist tetracyclines?

- Mutations to efflux pumps (TetA/B/C)

- Ribosome protection proteins (TetM/O)

What are the key points of tigecycline?

- Evades tet efflux and ribosomal protection resistance

- IV only

What are the key points of omadacycline (aminomethylcycline)?

- Used for CABP and acute bacterial skin infections

- IV and Oral

What are the key points of eravacycline (pyrrolidinoacetamide)?

- Potent against MDR Gram-negatives, including carbapenem-resistant Enterobacteriaceae

- IV only